The objective of the proposed research is to understand the pathogenesis of diffuse glomerular (i.e., glomerulonephritis and nephrotic syndrome) and diffuse tubulointerstitial nephritis in man through investigation of the nature and role of the glomerular mesangium in renal diseases; the effects of immunologic and biochemical injury on mesangial function; the factors that influence glomerular mesangial uptake and clearance of macromolecules, the relationship of glomerular mesangial function to increased glomerular capillary permeability to serum proteins, and the effects of immune tubular injury directed against Tamm-Horsfall protein on renal structure and function. The methods employed will include renal transplantation and renal perfusion in rats and quantitative determination of glomerular mesangial content of macromolecules, biochemical, radioisotope, histologic, immunopathologic and immunologic techniques.